The molecular and cellular mechanism of vasogenic edema in ischemic stroke remains to be fully elucidated. Inflammation initiated by ischemic brain injury may contribute to the development of vasogenic brain edema. The major findings in acute inflammation in tissue are: (1) accumulation of inflammatory mediators; (2) infiltration of inflammatory cells (polymorphonuclear cells and platelets); and (3) vascular injury with increased permeability. All these features have been noted in cerebral infarction. The putative mediators of vasogenic brain edema are also inflammatory mediators. We propose to investigate selected aspects of post-ischemic inflammatory reaction in an ischemic stroke model in the rat. The main focus of this proposal will be on the kinin-arachidonic acid cascade. We will characterize the activation of this cascade in relation to the evolution of brain edema, protein extravasation and polymorphonuclear cell infiltration. The roles of cellular and chemical mediators relevant to kinin-arachidonic acid cascade will be studied. The ultimate goal of this proposal is to develop new therapeutic regimens for treatment of ischemic brain edema which remains to be a major cause of death within one week of stroke onset.